Hyperalgesic Effect And Mechanisms To Chrysin In Mice

Chrysin (5, 7-dihydroxyflavone) is a natural flavone commonly found in many plants including Passiflora coerulea L. Researchers have made extensive and detailed investigations on the behavioral and pharmacological effects of chrysin in vivo, but there was scant information available on the effect of chrysin on the nociception. Therefore the present study was to investigate the effect of chrysin on the nociceptive threshold using the tail-immersion and hot-plate tests. Intraperitoneal (i.p.) injection of chrysin (10, 25, 50, 75, 100 mg/kg) dose- and time-dependently induced pronounced decrease of the tail withdrawl latencies (TWL), thus characterizing a hyperalgesic effect (ED₅₀ = 65.59 mg/kg). We also found that oral administration of chrysin (75 mg/kg) could produce a hyperalgesic effect in the tail-immersion test. The following results showed that GABA_A receptors were involved in the hyperalgesic effects of chrysin. (1) The hyperalgesia induced by chrysin was significantly and dose-dependently blocked by the pretreatment of flumazenil (0.75, 1 mg/kg, i.p.), a specific antagonist for benzodiazepine sites associated with GABA_A receptors. (2) Bicuculline (2, 4 mg/kg, i.p.), a GABA_A receptors antagonist, markedly antagonized the hyperalgesic effect of chrysin in a dose-dependent manner. (3) Picrotoxin (2 mg/kg, i.p.), a chloride channel blocker, could also notably antagonize the hyperalgesia of chrysin. (4) However, the pretreatment of opioid receptor antagonist naloxone (4 mg/kg, i.p.) did not significantly affect the hyperalgesic effect of chrysin. The nociceptive effect of chrysin was also tested with another pain model: hot-plate test. Chrysin dose-dependently produced a hyperalgesic effect and 75 mg/kg chrysin time-related produced a hyperalgesic effect in the hot-plate test. In addition, diazepam (1 mg/kg, i.p.) showed a marked antinociceptive effect, which was completely blocked by flumazenil (1 mg/kg, i.p.). In conclusion, both i.p. and oral administration of chrysin produced a significant hyperalgesic effect in the tail-immersion test. The same results were obtaied from the hot-plate test. The hyperalgesic effect of chrysin may be mediated by the GABA_A receptor and opioid receptor was not involved in.